1. Troglitazone, a PPAR agonist, inhibits human prostate cancer cell growth through inactivation of NFκB via suppression of GSK-3β expression
- Author
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Jung Ok Ban, Sang-Bae Han, Min Jong Song, Dohee Won, Jin Tae Hong, Ju Hoon Oh, Dong Cheul Moon, Seung Mo Son, Keon Wook Kang, and Ho Seub Song
- Subjects
Male ,Cancer Research ,medicine.medical_specialty ,Cell cycle checkpoint ,Immunoblotting ,Apoptosis ,Resting Phase, Cell Cycle ,chemistry.chemical_compound ,Prostate cancer ,Glycogen Synthase Kinase 3 ,Troglitazone ,Internal medicine ,Cell Line, Tumor ,LNCaP ,medicine ,Humans ,Urea ,Chromans ,Cell Proliferation ,Pharmacology ,Cell Nucleus ,Glycogen Synthase Kinase 3 beta ,Dose-Response Relationship, Drug ,Cell growth ,Cell Cycle ,G1 Phase ,NF-kappa B ,Prostatic Neoplasms ,medicine.disease ,PPAR gamma ,Thiazoles ,Endocrinology ,Oncology ,chemistry ,Microscopy, Fluorescence ,Cell culture ,Cancer cell ,Cancer research ,Molecular Medicine ,RNA Interference ,Thiazolidinediones ,Growth inhibition ,medicine.drug - Abstract
PPARγ ligands have been reported to reduce proliferation of human prostate cancer cells. However, the molecular mechanism of PPARγ agonist-induced cell growth inhibition of prostate cancer cells is not clear. GSK-3β expression and NFκB activity have important roles in prostate cancer development. To investigate the mechanisms of the PPARγ agonist-induced prostate cancer cell growth inhibition, we examined the effect of troglitazone on the expression of PPARγ, GSK-3β and activity of NFκB as well as on the prostate cancer cell growth. Troglitazone induced the expression of PPARγ in the nuclear of PC-3 cells, but not in LNCaP cells. Troglitazone (0-16 uM) inhibited cancer cell growth in a similar extend between both cells accompanied by the induction of cell cycle arrest in G(0)/G(1) phase and an increased in the similar extent of apoptotic cell death in concentration dependent manner. Troglitazone inhibited the constitutive expression of GSK-3β and activation of NFκB. Co-treatment of troglitazone with a GSK-3β inhibitor (AR-a014418) or GSK-3β siRNA significantly augmented the inhibitory effect of troglitazone on the NFκB activity and on prostate cancer cell growth inhibition and apoptotic cell death. However, overexpression of GSK-3β hindered troglitazone-induced cell growth inhibition and NFκB inactivation. These results suggest that PPARγ agonist, troglitazone, inhibits prostate cancer cell growth through inactivation of NFκB via suppression of GSK-3β expression.
- Published
- 2011